Clinical significance of histone deacetylase (HDAC)-1, HDAC-2, HDAC-4, and HDAC-6 expression in human malignant and benign thyroid lesions

Tumor Biology - Tập 35 - Trang 61-71 - 2013
Constantinos Giaginis1,2, Paraskevi Alexandrou1, Ioanna Delladetsima1, Ioanna Giannopoulou1, Efstratios Patsouris1, Stamatios Theocharis1
1First Department of Pathology, Medical School, University of Athens, Athens, Greece
2Department of Food Science and Nutrition, University of the Aegean, Myrina, Greece

Tóm tắt

Histone deacetylases (HDACs) have been associated with human malignant tumor development and progression, and HDAC inhibitors are currently being explored as anticancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression in human malignant and benign thyroid lesions. HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 74 patients with benign and malignant thyroid lesions. Enhanced HDAC-2 and HDAC-6 expression was significantly more frequently observed in malignant, compared to benign, thyroid lesions (p = 0.0042 and p = 0.0069, respectively). Enhanced HDAC-2, HDAC-4, and HDAC-6 expression was significantly more frequently observed in cases with papillary carcinoma compared to hyperplastic nodules (p = 0.0065, p = 0.0394, and p = 0.0061, respectively). In malignant thyroid lesions, HDAC-1, HDAC-4, and HDAC-6 expression was significantly associated with tumor size (p = 0.0169, p = 0.0056, and p = 0.0234, respectively); HDAC-2 expression with lymphatic and vascular invasion (p = 0.0299 and p = 0.0391, respectively); and HDAC-4 expression with capsular invasion (p = 0.0464). The cellular pattern of HDAC-1 and HDAC-2 distribution (nuclear vs. nuclear and cytoplasmic) presented a distinct discrimination between malignant and benign thyroid lesions (p = 0.0030 and p = 0.0028, respectively) as well as between papillary carcinoma and hyperplastic nodules (p = 0.0036 and p = 0.0028, respectively). HDAC-1, HDAC-2, HDAC-4, and HDAC-6 may be associated with the malignant thyroid transformation and could be considered as useful biomarkers and possible therapeutic targets in this neoplasia.

Tài liệu tham khảo

Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French Thyroid Cancer Committee. Thyroid. 2004;14:1056–60.

Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.

Ward EM, Jemal A, Chen A. Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole explanation? Future Oncol. 2010;6:185–8.

Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer. 1998;83:2638–48.

Segev DL, Umbricht C, Zeiger MA. Molecular pathogenesis of thyroid cancer. Surg Oncol. 2003;12:69–90.

Gharib H, Papini E. Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin North Am. 2007;36:707–35.

Schlumberger M, Lacroix L, Russo D, Filetti S, Bidart JM. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nat Clin Pract Endocrinol Metab. 2007;3:260–9.

Stang MT, Carty SE. Recent developments in predicting thyroid malignancy. Curr Opin Oncol. 2009;21:11–7.

Fischer S, Asa L. Application of immunohistochemistry to thyroid neoplasms. Arch Pathol Lab Med. 2008;132:359–72.

Besic N, Sesek M, Peric B, et al. Predictive factors of carcinoma in 327 patients with follicular neoplasm of the thyroid. Med Sci Monit. 2008;14:CR459–67.

Vriens MR, Schreinemakers JM, Suh I, et al. Diagnostic markers and prognostic factors in thyroid cancer. Future Oncol. 2009;5:1283–93.

Aisner DL, Sams SB. The role of cytology specimens in molecular testing of solid tumors: techniques, limitations, and opportunities. Diagn Cytopathol. 2012;40:511–24.

Morales V, Giamarchi C, Chailleux C, et al. Chromatin structure and dynamics: functional implications. Biochimie. 2001;83:1029–39.

Marks P, Rifkind RA, Richon VM, et al. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1:194–202.

Grozinger CM, Schreiber SL. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. Chem Biol. 2002;9:3–16.

Glozak MA, Seto E. Histone deacetylases and cancer. Oncogene. 2007;26:5420–32.

Tan J, Cang S, Ma Y, et al. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol. 2010;3:5.

Kouraklis G, Theocharis S. Histone deacetylase inhibitors: a novel target of anticancer therapy (review). Oncol Rep. 2006;15:489–94.

Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol. 2009;27:5459–68.

Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5:769–84.

Ma X, Ezzeldin HH, Diasio RB. Histone deacetylase inhibitors: current status and overview of recent clinical trials. Drugs. 2009;69:1911–34.

Molife LR, de Bono JS. Belinostat: clinical applications in solid tumors and lymphoma. Expert Opin Investig Drugs. 2011;20:1723–32.

Brosch G, Loidl P, Graessle S. Histone modifications and chromatin dynamics: a focus on filamentous fungi. FEMS Microbiol Rev. 2008;32:409–39.

Khan O, La Thangue NB. HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol Cell Biol. 2012;90:85–94.

Halkidou K, Gaughan L, Cook S. Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate. 2004;59:177–89.

Weichert W, Denkert C, Noske A, et al. Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia. 2008;10:1021–7.

Weichert W, Roske A, Gekeler V, et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9:139–48.

Weichert W, Roske A, Niesporek S, et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14:1669–77.

Fritzsche FR, Weichert W, Röske A, et al. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer. 2008;8:381.

Wang W, Gao J, Man XH, et al. Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer. Oncol Rep. 2009;21:1439–47.

Rikimaru T, Taketomi A, Yamashita Y, et al. Clinical significance of histone deacetylase 1 expression in patients with hepatocellular carcinoma. Oncology. 2007;72:69–74.

Sasaki H, Moriyama S, Nakashima Y, et al. Histone deacetylase 1 mRNA expression in lung cancer. Lung Cancer. 2004;46:171–8.

Krusche CA, Wulfing P, Kersting C, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat. 2005;90:15–23.

Zhang Z, Yamashita H, Toyama T, et al. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Breast Cancer Res Treat. 2005;94:11–6.

Marquard L, Gjerdrum LM, Christensen IJ. Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma. Histopathology. 2008;53:267–77.

Marquard L, Poulsen CB, Gjerdrum LM, et al. Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas. Histopathology. 2009;54:688–98.

Oehme I, Deubzer HE, Wegener D, et al. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin Cancer Res. 2009;15:91–9.

Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett. 2009;280:168–76.

Rosai J, Appendix C. Staging of cancer. In: Houston M, editor. Rosai and Ackerman's Surgical Pathology. 9th ed. London: Mosby; 2004. p. 2809–10.

Tuttle RM, Tala H, Shah J, et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010;20:1341.

Theocharis S, Klijanienko J, Giaginis C, et al. Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. J Oral Pathol Med. 2011;40:706–14.

Michailidi C, Giaginis C, Stolakis V, et al. Evaluation of FAK and Src expression in human benign and malignant thyroid lesions. Pathol Oncol Res. 2010;16:497–507.

Giaginis C, Michailidi C, Stolakis V, et al. Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: an immunohistochemical study. Med Sci Monit. 2011;17:BR81–90.

Giaginis C, Demetriou N, Alexandrou P, et al. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) expression in human benign and malignant thyroid lesions. Med Sci Monit. 2012;18:BR123–9.

Karidis NP, Giaginis C, Tsourouflis G, et al. Eph-A2 and Eph-A4 expression in human benign and malignant thyroid lesions: an immunohistochemical study. Med Sci Monit. 2011;17:BR257–65.

Kondo T, Asa SL, Ezzat S. Epigenetic dysregulation in thyroid neoplasia. Endocrinol Metab Clin North Am. 2008;37:389–400.

Russo D, Damante G, Puxeddu E, Durante C, Filetti S. Epigenetics of thyroid cancer and novel therapeutic targets. J Mol Endocrinol. 2011;46(3):R73–81.

Russo D, Durante C, Bulotta S, Puppin C, Puxeddu E, Filetti S, et al. Targeting histone deacetylase in thyroid cancer. Expert Opin Ther Targets. 2013;17:179–93.

Mitmaker EJ, Griff NJ, Grogan RH, et al. Modulation of matrix metalloproteinase activity in human thyroid cancer cell lines using demethylating agents and histone deacetylase inhibitors. Surgery. 2011;149:504–11.

Altmann A, Eisenhut M, Bauder-Wüst U. Therapy of thyroid carcinoma with the histone deacetylase inhibitor MS-275. Eur J Nucl Med Mol Imaging. 2010;37:2286–97.

McKinsey TA, Zhang CL, Olson EN. Identification of a signal responsive nuclear export sequence in class II histone deacetylases. Mol Cell Biol. 2001;21:6312–21.

Kao HY, Verdel A, Tsai CC, et al. Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7. J Biol Chem. 2001;276:47496–507.

Calalb MB, McKinsey TA, Newkirk S, et al. Increased phosphorylation-dependent nuclear export of class II histone deacetylases in failing human heart. Clin Transl Sci. 2009;2:325–32.

Langley E, Pearson M, Faretta M. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002;21:2383–96.

Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: versatile regulators. Trends Genet. 2003;19:286–93.

Thông tin
Thông tin xuất bản

Tumor Biology

Tập 35

61-71

Thông tin tác giả